Prognostic significance of EZH2 and ARID1A expression in urothelial carcinoma: an immunohistochemical study.

Abstract

Enhancer of zeste homolog 2 (EZH2) and AT-rich interactive domain 1A (ARID1A) expression in urothelial carcinoma (UC) has not been well studied. ARID1A is a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in urinary bladder cancer. The enhancer of zeste homolog 2 (EZH2) is a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies. This study analyzed the immunohistochemical expression of EZH2 and ARID1A in 56 cases of UC that included (n = 21) cases of radical cystectomy and (n = 35) cases of transurethral resections of bladder tumor (TURBT) with muscle fibers and immunotherapy with adjuvant intravesical bacillus Calmette-Guerin (BCG). The predicting role of both markers for tumor recurrence and recurrence-free survival (RFS) was also analyzed. High EZH2 marker expression was observed in 75% of cases while 78.6% of cases had low ARID1A marker expression. There was a significant negative correlation between the two markers where high EZH2 and low ARID1A expression was significantly associated with higher tumor grade, stage, presence of muscle invasion, lymph node metastasis, presence of concomitant carcinoma in situ (CIS) and higher incidence of recurrence with shorter RFS rate. It was concluded that EZH2 and ARID1A play a role in tumor carcinogenesis and differentiation and could be considered as independent prognostic factors in UC and for use as a potential therapeutic target.